FAM135B

Summary

FAM135B (family with sequence similarity 135 member B, HGNC:28029) is a protein-coding gene on chromosome 8q24.23, encoding Protein FAM135B (Q49AJ0).

Predicted to be involved in lipid metabolic process.

Source: NCBI Gene 51059 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 213 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 6 cancer types
• MANE Select transcript: NM_015912

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28029
Approved symbol	FAM135B
Name	family with sequence similarity 135 member B
Location	8q24.23
Locus type	gene with protein product
Status	Approved
Aliases	C8ORFK32
Ensembl gene	ENSG00000147724
Ensembl biotype	protein_coding
Entrez	51059

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 4 protein_coding_CDS_not_defined, 3 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000160713, ENST00000276737, ENST00000395295, ENST00000395297, ENST00000467365, ENST00000482951, ENST00000517849, ENST00000520283, ENST00000520380, ENST00000520954, ENST00000523049

RefSeq mRNA: 2 — MANE Select: NM_015912 NM_001362965, NM_015912

CCDS: CCDS6375

Canonical transcript exons

ENST00000395297 — 20 exons

Exon	Start	End
ENSE00001664480	138130023	138132798
ENSE00003477538	138148520	138148686
ENSE00003483857	138143012	138143109
ENSE00003494999	138197516	138197669
ENSE00003497311	138367907	138368002
ENSE00003509020	138242942	138243068
ENSE00003548854	138167895	138168049
ENSE00003556687	138265703	138265842
ENSE00003561057	138137147	138137260
ENSE00003569938	138195258	138195307
ENSE00003593326	138310841	138310920
ENSE00003597627	138177347	138177420
ENSE00003608752	138256689	138256759
ENSE00003624556	138250841	138251014
ENSE00003629289	138138986	138139096
ENSE00003640455	138141198	138141349
ENSE00003645663	138151194	138153216
ENSE00003659390	138178535	138178690
ENSE00003660634	138145959	138146050
ENSE00003841670	138496671	138497261

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 82.38.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7814 / max 91.8156, expressed in 122 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95286	0.3361	108
95285	0.2388	86
95283	0.1756	85
95284	0.0216	11
95282	0.0092	5

Top tissues by expression

238 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	82.38	gold quality
sperm	CL:0000019	82.33	gold quality
right testis	UBERON:0004534	81.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.29	gold quality
testis	UBERON:0000473	79.76	gold quality
cortical plate	UBERON:0005343	78.03	gold quality
cerebellar hemisphere	UBERON:0002245	77.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.50	gold quality
cerebellar cortex	UBERON:0002129	77.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.08	gold quality
sural nerve	UBERON:0015488	76.93	gold quality
pancreatic ductal cell	CL:0002079	76.91	silver quality
cerebellum	UBERON:0002037	76.10	gold quality
islet of Langerhans	UBERON:0000006	75.95	gold quality
prefrontal cortex	UBERON:0000451	75.57	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.81	gold quality
right frontal lobe	UBERON:0002810	73.45	gold quality
frontal cortex	UBERON:0001870	71.82	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	71.44	gold quality
neocortex	UBERON:0001950	71.43	gold quality
anterior cingulate cortex	UBERON:0009835	71.25	gold quality
cerebral cortex	UBERON:0000956	68.86	gold quality
caudate nucleus	UBERON:0001873	68.63	gold quality
oocyte	CL:0000023	68.26	gold quality
primary visual cortex	UBERON:0002436	68.02	gold quality
putamen	UBERON:0001874	67.93	gold quality
corpus callosum	UBERON:0002336	67.79	gold quality
brain	UBERON:0000955	67.58	gold quality
nucleus accumbens	UBERON:0001882	67.40	gold quality
forebrain	UBERON:0001890	66.93	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

135 targeting FAM135B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-515-5P	99.92	69.82	2343

Literature-anchored findings (GeneRIF, showing 3)

• Using microarray analysis reveals novel genes such as FAM135B, dysregulated in Spinal and bulbar muscular atrophy (SBMA). Knockdown of FAM135B results in neurodegeneration, indicating its role in SBMA. (PMID:30391288)
• A GRN Autocrine-Dependent FAM135B/AKT/mTOR Feedforward Loop Promotes Esophageal Squamous Cell Carcinoma Progression. (PMID:33323378)
• Silencing FAM135B enhances radiosensitivity of esophageal carcinoma cell. (PMID:33340561)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000105121
mus_musculus	Fam135b	ENSMUSG00000036800
rattus_norvegicus	Fam135b	ENSRNOG00000005159
drosophila_melanogaster	CG32333	FBGN0052333
caenorhabditis_elegans	C09D4.4	WBGENE00015635

Paralogs (1): FAM135A (ENSG00000082269)

Protein

Protein identifiers

Protein FAM135B — Q49AJ0 (reviewed: Q49AJ0)

All UniProt accessions (4): Q49AJ0, E5RFQ7, E5RH68, J3QSR3

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the FAM135 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q49AJ0-1	1	yes
Q49AJ0-2	2
Q49AJ0-3	3
Q49AJ0-4	4

RefSeq proteins (2): NP_001349894, NP_056996* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007751	DUF676_lipase-like	Domain
IPR022122	DUF3657	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR044294	Lipase-like	Family

Pfam: PF05057, PF12394

UniProt features (17 total): splice variant 5, sequence variant 4, region of interest 2, sequence conflict 2, modified residue 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q49AJ0-F1	62.14	0.34

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 777, 778

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 55 (showing top): FREAC2_01, HATADA_METHYLATED_IN_LUNG_CANCER_DN, TGANTCA_AP1_C, GOBP_LIPID_METABOLIC_PROCESS, MODULE_48, MODULE_95, HOXA4_Q2, chr8q24, RATTENBACHER_BOUND_BY_CELF1, MODULE_163, GSE13547_CTRL_VS_ANTI_IGM_STIM_BCELL_2H_DN, PAX3_TARGET_GENES, SUPT16H_TARGET_GENES, ZNF7_TARGET_GENES, MIR1277_5P

GO Biological Process (1): lipid metabolic process (GO:0006629)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
binding	1

Protein interactions and networks

STRING

644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM135B	ADAM29	Q9UKF5	663
FAM135B	CSMD3	Q7Z407	476
FAM135B	SLC6A17	Q9H1V8	473
FAM135B	LRP1B	Q9NZR2	456
FAM135B	ZNF750	Q32MQ0	450
FAM135B	FAT1	Q14517	449
FAM135B	ZFHX4	Q86UP3	444
FAM135B	FAT2	Q9NYQ8	412
FAM135B	ZNF610	Q8N9Z0	411
FAM135B	NXPH2	O95156	410
FAM135B	XIRP2	A4UGR9	401
FAM135B	KDELR2	P33947	397
FAM135B	LRIG3	Q6UXM1	393
FAM135B	SPTA1	P02549	392
FAM135B	PPP1R42	Q7Z4L9	385

IntAct

5 interactions, top by confidence:

A	B	Type	Score
FAM135B	ZDHHC17	psi-mi:“MI:0915”(physical association)	0.570
FAM135B	FYN	psi-mi:“MI:0914”(association)	0.350
FAM135B	KAT5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): FAM135B (Two-hybrid), ZDHHC17 (Affinity Capture-MS), ZDHHC17 (Affinity Capture-MS), KAT5 (Two-hybrid), ZDHHC17 (Affinity Capture-MS), STK26 (Affinity Capture-MS), FYN (Affinity Capture-MS), FAM135B (Proximity Label-MS), FAM135B (Affinity Capture-MS), MRC2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1L8EYB2, A0JMF7, A2AHC3, A3KMW7, A5D8S0, A5WUN7, B0S6S9, D3Z8E6, D3Z987, F1M5M3, F1MJR8, F1QB81, P70347, P97412, Q0P5X5, Q0VET5, Q15468, Q2M2Z5, Q2T9I9, Q3UEN2, Q3V0M2, Q49A88, Q49AJ0, Q5CZC0, Q5RA75, Q5RHB5, Q5SW75, Q5T5Y3, Q60664, Q6JPI3, Q6NRK3, Q6PUR7, Q71F56, Q76I76, Q7M6U3, Q7TSH4, Q8C753, Q8CCC3, Q8IWB6, Q8K2J4

Diamond homologs: Q49AJ0, Q5RA75, Q641I1, Q6NS59, Q9DAI6, Q9P2D6

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 6 cancer types — HNSC, LUSC, PAAD, UCEC, UCS, WDTC.

Clinical variants and AI predictions

ClinVar

213 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	179
Likely benign	17
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

4494 predictions. Top by Δscore:

Variant	Effect	Δscore
8:138138981:CTGA:C	donor_loss	1.0000
8:138138982:TGA:T	donor_loss	1.0000
8:138138983:GAC:G	donor_loss	1.0000
8:138138984:A:C	donor_loss	1.0000
8:138138985:C:A	donor_loss	1.0000
8:138139092:TAAGC:T	acceptor_gain	1.0000
8:138139094:AGC:A	acceptor_gain	1.0000
8:138139094:AGCC:A	acceptor_loss	1.0000
8:138139095:GCC:G	acceptor_loss	1.0000
8:138139096:CCTA:C	acceptor_loss	1.0000
8:138139098:T:A	acceptor_loss	1.0000
8:138141193:CTTA:C	donor_loss	1.0000
8:138141195:TACCT:T	donor_loss	1.0000
8:138141345:TGAAG:T	acceptor_gain	1.0000
8:138141346:GAAG:G	acceptor_gain	1.0000
8:138141347:AAG:A	acceptor_gain	1.0000
8:138141347:AAGCT:A	acceptor_loss	1.0000
8:138141348:AG:A	acceptor_gain	1.0000
8:138141348:AGC:A	acceptor_loss	1.0000
8:138141349:GC:G	acceptor_loss	1.0000
8:138141350:C:CA	acceptor_loss	1.0000
8:138141350:C:CC	acceptor_gain	1.0000
8:138141351:T:G	acceptor_loss	1.0000
8:138141352:G:C	acceptor_gain	1.0000
8:138141352:G:GC	acceptor_gain	1.0000
8:138143108:ATC:A	acceptor_loss	1.0000
8:138148514:ACT:A	donor_loss	1.0000
8:138148515:CTC:C	donor_loss	1.0000
8:138148516:TCA:T	donor_loss	1.0000
8:138148517:CACCA:C	donor_loss	1.0000

AlphaMissense

9253 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:138139096:C:T	G1264D	1.000
8:138141308:A:T	V1227D	1.000
8:138141330:C:G	G1220R	1.000
8:138148543:A:T	V1142D	1.000
8:138148546:A:G	L1141P	1.000
8:138137233:A:G	L1310P	0.999
8:138137239:A:T	V1308D	0.999
8:138139000:A:G	L1296P	0.999
8:138139048:A:G	L1280P	0.999
8:138139075:A:G	L1271P	0.999
8:138139087:A:G	L1267P	0.999
8:138141198:C:G	G1264R	0.999
8:138141246:C:A	G1248W	0.999
8:138141257:A:G	L1244P	0.999
8:138141290:A:G	F1233S	0.999
8:138141329:C:A	G1220V	0.999
8:138141329:C:T	G1220D	0.999
8:138141341:C:T	G1216D	0.999
8:138141347:A:G	F1214S	0.999
8:138141349:G:C	S1213R	0.999
8:138141349:G:T	S1213R	0.999
8:138143013:T:G	S1213R	0.999
8:138143069:A:G	L1194S	0.999
8:138145978:A:G	L1174P	0.999
8:138145980:G:C	F1173L	0.999
8:138145980:G:T	F1173L	0.999
8:138145981:A:G	F1173S	0.999
8:138145982:A:G	F1173L	0.999
8:138146035:A:G	L1155P	0.999
8:138148520:C:A	G1150W	0.999

dbSNP variants (sampled 300 via entrez): RS1000011556 (8:138337660 T>C), RS1000021880 (8:138499074 T>A,C), RS1000023605 (8:138190860 A>G), RS1000029613 (8:138176277 C>A,G,T), RS1000032525 (8:138273626 G>T), RS1000036280 (8:138329023 C>T), RS1000042411 (8:138416696 T>C,G), RS1000046723 (8:138288755 A>G), RS1000048109 (8:138451535 C>G), RS1000066047 (8:138411492 G>C,T), RS1000077235 (8:138411153 T>G), RS1000080049 (8:138199142 A>C), RS1000083236 (8:138342464 G>A,C), RS1000088720 (8:138181794 A>G), RS1000090507 (8:138496162 C>G,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000579_47	Cognitive performance	2.000000e-06
GCST000579_55	Cognitive performance	5.000000e-06
GCST001371_13	Inflammatory biomarkers	2.000000e-06
GCST002136_17	Periodontitis (PAL4Q3)	9.000000e-06
GCST004029_35	Angiotensin-converting enzyme inhibitor intolerance	9.000000e-06
GCST005359_15	Disease progression in age-related macular degeneration	8.000000e-06
GCST008361_1	Response to cognitive-behavioural therapy in major depressive disorder	1.000000e-06
GCST008477_12	Emphysema annual change measurement in smokers (adjusted lung density)	5.000000e-06
GCST008477_30	Emphysema annual change measurement in smokers (adjusted lung density)	3.000000e-06
GCST008822_7	Neuritic plaque	9.000000e-06
GCST009174_1	Response to (pegylated) interferon in chronic hepatitis B	6.000000e-07
GCST009391_1079	Metabolite levels	4.000000e-06
GCST010483_5	Cardiovascular death, myocardial infarction or stroke in response to clopidogrel treatment	4.000000e-06

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0008336	disease progression measurement
EFO:0007820	cognitive behavioural therapy
EFO:0007626	emphysema imaging measurement
EFO:0006798	neuritic plaque measurement
EFO:0007859	response to interferon
EFO:0010529	ribose-5-phosphate measurement
EFO:0010530	ribulose-5-phosphate measurement
EFO:0006919	cardiovascular event measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Niclosamide	increases expression	1
Valproic Acid	decreases expression	1
Aflatoxin B1	increases methylation	1
Sodium Selenite	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.